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Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues

Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis re...

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Autores principales: Xu, Yingjiang, Shi, Ting, Cui, Xuan, Yan, Linyu, Wang, Qi, Xu, Xiaoyan, Zhao, Qingwen, Xu, Xiaoxuan, Tang, Qi‐Qun, Tang, Huiru, Pan, Dongning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672174/
https://www.ncbi.nlm.nih.gov/pubmed/34704268
http://dx.doi.org/10.15252/embj.2021108069
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author Xu, Yingjiang
Shi, Ting
Cui, Xuan
Yan, Linyu
Wang, Qi
Xu, Xiaoyan
Zhao, Qingwen
Xu, Xiaoxuan
Tang, Qi‐Qun
Tang, Huiru
Pan, Dongning
author_facet Xu, Yingjiang
Shi, Ting
Cui, Xuan
Yan, Linyu
Wang, Qi
Xu, Xiaoyan
Zhao, Qingwen
Xu, Xiaoxuan
Tang, Qi‐Qun
Tang, Huiru
Pan, Dongning
author_sort Xu, Yingjiang
collection PubMed
description Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine‐fed mice showed better cold tolerance. In mice with diet‐induced obesity, the asparagine‐fed group was more responsive to β3‐adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and (13)C‐glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis.
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spelling pubmed-86721742021-12-30 Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues Xu, Yingjiang Shi, Ting Cui, Xuan Yan, Linyu Wang, Qi Xu, Xiaoyan Zhao, Qingwen Xu, Xiaoxuan Tang, Qi‐Qun Tang, Huiru Pan, Dongning EMBO J Articles Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine‐fed mice showed better cold tolerance. In mice with diet‐induced obesity, the asparagine‐fed group was more responsive to β3‐adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and (13)C‐glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis. John Wiley and Sons Inc. 2021-10-27 2021-12-15 /pmc/articles/PMC8672174/ /pubmed/34704268 http://dx.doi.org/10.15252/embj.2021108069 Text en © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Xu, Yingjiang
Shi, Ting
Cui, Xuan
Yan, Linyu
Wang, Qi
Xu, Xiaoyan
Zhao, Qingwen
Xu, Xiaoxuan
Tang, Qi‐Qun
Tang, Huiru
Pan, Dongning
Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
title Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
title_full Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
title_fullStr Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
title_full_unstemmed Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
title_short Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
title_sort asparagine reinforces mtorc1 signaling to boost thermogenesis and glycolysis in adipose tissues
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672174/
https://www.ncbi.nlm.nih.gov/pubmed/34704268
http://dx.doi.org/10.15252/embj.2021108069
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